دانلود رایگان مقاله انگلیسی ارتباط بین تغییرات در اختلال ژن اسکیزوفرنی 1 و اسکیزوفرنی - الزویر 2018

Abstract

Schizophrenia is a severe psychiatric disorder. Genetic and functional studies have strongly implicated the disrupted in schizophrenia 1 gene (DISC1) as a candidate susceptibility gene for schizophrenia. Moreover, recent association studies have indicated that several DISC1 single nucleotide polymorphisms (SNPs) are associated with schizophrenia. However, the association is hardly replicate in different ethnic group. Here, we performed a meta-analysis of the association between DISC1 SNPs and schizophrenia in which the samples were divided into subgroups according to ethnicity. Both rs3738401 and rs821616 showed not significantly association with schizophrenia in the Caucasian, Asian, Japanese or Han Chinese populations.

Discussion

The present meta-analysis analyzed the association between DISC1 SNPs rs3738401 and rs821616 with schizophrenia. We found that rs3738401 did not show association with schizophrenia in the Caucasian, Asian or Japanese subgroups. Like rs3738401, no positive association was identified between rs821616 and schizophrenia in Caucasian, Asian, Japanese or Han Chinese subjects, which is consistent with the two previous meta-analyses conducted by Mathieson et al. and Kinoshita et al. in Caucasian and Japanese populations, respectively (Kinoshita et al., 2012; Mathieson et al., 2012). DISC1 is located at chromosomal breakpoint 1q42.1. Compared with such major gene interruptions, the contribution of SNPs to the pathogenesis of schizophrenia may only be minor, even if the SNP is located in a coding region (Bae et al., 2013). However, considering the much higher frequency of SNPs relative to translocations, there is still a need to analyze the association of DISC1 SNPs with schizophrenia. Many previous genetic studies have investigated the association between DISC1 and schizophrenia; however, the results are inconsistent, including SNP and haplotype findings. Previous meta-analyses failed to identify positive associations between DISC1 variants and schizophrenia (Kinoshita et al., 2012; Mathieson et al., 2012), although differences in sample sizes, population, allelic heterogeneity, or genetic heterogeneity of disease could all cause difficulties in replicating data (Munafo and Flint, 2004). Considering the allelic heterogeneity and different genetic background between Caucasians and Asians, we divided the studies included in our meta-analysis into subgroups based on the ethnic population to minimize heterogeneity. However, rs3738401 and rs821616 showed no association with schizophrenia either in the Caucasian or Asian subgroup. Since gene expression regulated by genetic variants shows difference between Japanese and Han Chinese (Yuan et al., 2013), we divided Asia population into Japanese and Han Chinese subgroups with more specific. However, the association between rs3738401 or rs821616 and schizophrenia was still not found.